The Central Nervous System

The mature mammalian central nervous system (CNS) is composed of three major differentiated cell types: neurons, astrocytes and oligodendrocytes. Neurons transmit information through action potentials and neurotransmitters to other neurons, muscle cells or gland cells. Astrocytes and oligodendrocytes, collectively called glial cells, play important roles of their own, in addition to providing a critical support role for optimal neuronal functioning and survival. During mammalian embryogenesis, CNS development begins with the induction of the neuroectoderm, which forms the neural plate and then folds to give rise to the neural tube. Within these neural structures there exists a complex and heterogeneous population of neuroepithelial progenitor cells (NEPs), the earliest neural stem cell type to form.1,2 As CNS development proceeds, NEPs give rise to temporally and spatially distinct neural stem/progenitor populations. During the early stage of neural development, NEPs undergo symmetric divisions to expand neural stem cell (NSC) pools. In the later stage of neural development, NSCs switch to asymmetric division cycles and give rise to lineage-restricted progenitors. Intermediate neuronal progenitor cells are formed first, and these subsequently differentiate to generate to neurons. Following this neurogenic phase, NSCs undergo asymmetric divisions to produce glial-restricted progenitors, which generate astrocytes and oligodendrocytes. The later stage of CNS development involves a period of axonal pruning and neuronal apoptosis, which fine tunes the circuitry of the CNS. A previously long-held dogma maintained that neurogenesis in the adult mammalian CNS was complete, rendering it incapable of mitotic divisions to generate new neurons, and therefore lacking in the ability to repair damaged tissue caused by diseases (e.g. Parkinsons disease, multiple sclerosis) or injuries (e.g. spinal cord and brain ischemic injuries). However, there is now strong evidence that multipotent NSCs do exist, albeit only in specialized microenvironments, in the mature mammalian CNS. This discovery has fuelled a new era of research into understanding the tremendous potential that these cells hold for treatment of CNS diseases and injuries.

Neurobiologists routinely use various terms interchangeably to describe undifferentiated cells of the CNS. The most commonly used terms are stem cell, precursor cell and progenitor cell. The inappropriate use of these terms to identify undifferentiated cells in the CNS has led to confusion and misunderstandings in the field of NSC and neural progenitor cell research. However, these different types of undifferentiated cells in the CNS technically possess different characteristics and fates. For clarity, the terminology used here is:

Neural Stem Cell (NSCs): Multipotent cells which are able to self-renew and proliferate without limit, to produce progeny cells which terminally differentiate into neurons, astrocytes and oligodendrocytes. The non-stem cell progeny of NSCs are referred to as neural progenitor cells.

Neural Progenitor Cell: Neural progenitor cells have the capacity to proliferate and differentiate into more than one cell type. Neural progenitor cells can therefore be unipotent, bipotent or multipotent. A distinguishing feature of a neural progenitor cell is that, unlike a stem cell, it has a limited proliferative ability and does not exhibit self-renewal.

Neural Precursor Cells (NPCs): As used here, this refers to a mixed population of cells consisting of all undifferentiated progeny of neural stem cells, therefore including both neural progenitor cells and neural stem cells. The term neural precursor cells is commonly used to collectively describe the mixed population of NSCs and neural progenitor cells derived from embryonic stem cells and induced pluripotent stem cells.

Prior to 1992, numerous reports demonstrated evidence of neurogenesis and limited in vitro proliferation of neural progenitor cells isolated from embryonic tissue in the presence of growth factors.3-5 While several sub-populations of neural progenitor cells had been identified in the adult CNS, researchers were unable to demonstrate convincingly the characteristic features of a stem cell, namely self-renewal, extended proliferative capacity and retention of multi-lineage potential. In vivo studies supported the notion that proliferation occurred early in life, whereas the adultCNS was mitotically inactive, and unable to generate new cells following injury. Notable exceptions included several studies in the 1960s that clearly identified a region of the adult brain that exhibited proliferation (the forebrain subependyma)6 but this was believed to be species-specific and was not thought to exist in all mammals. In the early 1990s, cells that responded to specific growth factors and exhibited stem cell features in vitro were isolated from the embryonic and adult CNS.7-8 With these studies, Reynolds and Weiss demonstrated that a rare population of cells in the adult CNS exhibited the defining characteristics of a stem cell: self-renewal, capacity to produce a large number of progeny and multilineage potential. The location of stem cells in the adult brain was later identified to be within the striatum,9 and researchers began to show that cells isolated from this region, and the dorsolateral region of the lateral ventricle of the adult brain, were capable of differentiating into both neurons and glia.10

During mammalian CNS development, neural precursor cells arising from the neural tube produce pools of multipotent and more restricted neural progenitor cells, which then proliferate, migrate and further differentiate into neurons and glial cells. During embryogenesis, neural precursor cells are derived from the neuroectoderm and can first be detected during neural plate and neural tube formation. As the embryo develops, neural stem cells can be identified in nearly all regions of the embryonic mouse, rat and human CNS, including the septum, cortex, thalamus, ventral mesencephalon and spinal cord. NSCs isolated from these regions have a distinct spatial identity and differentiation potential. In contrast to the developing nervous system, where NSCs are fairly ubiquitous, cells with neural stem cell characteristics are localized primarily to two key regions of the mature CNS: the subventricular zone (SVZ), lining the lateral ventricles of the forebrain, and the subgranular layer of thedentate gyrus of the hippocampal formation (described later).11 In the adult mouse brain, the SVZ contains a heterogeneous population of proliferating cells. However, it is believed that the type B cells (activated GFAP+/PAX6+ astrocytes or astrogliallike NSCs) are the cells that exhibit stem cell properties, and these cells may be derived directly from radial glial cells, the predominant neural precursor population in the early developing brain. NPCs in this niche are relatively quiescent under normal physiological conditions, but can be induced to proliferate and to repopulate the SVZ following irradiation.10 SVZ NSCs maintain neurogenesis throughout adult life through the production of fast-dividing transit amplifying progenitors (TAPs or C cells), which then differentiate and give rise to neuroblasts. TAPs and neuroblasts migrate through the rostral migratory stream (RMS) and further differentiate into new interneurons in the olfactory bulb. This ongoing neurogenesis, which is supported by the NSCs in the SVZ, is essential for maintenance of the olfactory system, providing a source of new neurons for the olfactory bulb of rodents and the association cortex of non-human primates.12 Although the RMS in the adult human brain has been elusive, a similar migration of neuroblasts through the RMS has also been observed.13 Neurogenesis also persists in the subgranular zone of the hippocampus, a region important for learning and memory, where it leads to the production of new granule cells. Lineage tracing studies have mapped the neural progenitor cells to the dorsal region of the hippocampus, in a collapsed ventricle within the dentate gyrus.10 Studies have demonstrated that neurogenic cells from the subgranular layer may have a more limited proliferative potential than the SVZ NSCs and are more likely to be progenitor cells than true stem cells.14 Recent evidence also suggests that neurogenesis plays a different role in the hippocampus than in the olfactory bulb. Whereas the SVZ NSCs play a maintenance role, it is thought that hippocampal neurogenesis serves to increase the number of new neurons and contributes to hippocampal growth throughout adult life.12 Neural progenitor cells have also been identified in the spinal cord central canal ventricular zone and pial boundary15-16, and it is possible that additional regional progenitor populations will be identified in the future.

In vitro methodologies designed to isolate, expand and functionally characterize NSC populations have revolutionized our understanding of neural stem cell biology, and increased our knowledge of the genetic and epigenetic regulation of NSCs.17 Over the past several decades, a number of culture systems have been developed that attempt to recapitulate the distinct in vivo developmental stages of the nervous system, enabling theisolation and expansion of different NPC populations at different stages of development. Here, we outline the commonly used culture systems for generating NPCs from pluripotent stem cells (PSCs), and for isolating and expanding NSCs from the early embryonic, postnatal and adult CNS.

Neural induction and differentiation of pluripotent stem cells: Early NPCs can be derived from mouse and human PSCs, which include embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), using appropriate neural induction conditions at the first stage of differentiation. While these neural differentiation protocols vary widely, a prominent feature in popular embryoid body-based protocols is the generation of neural rosettes, morphologically identifiable structures containing NPCs, which are believed to represent the neural tube. The NPCs present in the neural rosette structures are then isolated, and can be propagated to allow NPC expansion, while maintaining the potential to generate neurons and glial cells. More recently, studies have shown that neural induction of PSCs can also be achieved in a monolayer culture system, wherein human ESCs and iPSCs are plated onto a defined matrix, and exposed to inductive factors.18 A combination of specific cytokines or small molecules, believed to mimic the developmental cues for spatiotemporal patterning in the developing brain during embryogenesis, can be added to cultures at the neural induction stage to promote regionalization of NPCs. These patterned NPCs can then be differentiated into mature cell types with phenotypes representative of different regions of the brain.19-24 New protocols have been developed to generate cerebral organoids from PSC-derived neural progenitor cells. Cerebral organoids recapitulate features of human brain development, including the formation of discrete brain regions featuring characteristic laminar cellular organization.25

Neurosphere culture: The neurosphere culture system has been widely used since its development as a method to identify NSCs.26-29 A specific region of the CNS is microdissected, mechanically or enzymatically dissociated, and plated in adefined serum-free medium in the presence of a mitogenic factor, such as epidermal growth factor (EGF) and/or basic fibroblast growth factor (bFGF). In the neurosphere culture system, NSCs, as well as neural progenitor cells, begin to proliferate in response to these mitogens, forming small clusters of cells after 2 - 3 days. The clusters continue to grow in size, and by day 3 - 5, the majority of clusters detach from the culture surface and begin to grow in suspension. By approximately day seven, depending on the cell source, the cell clusters, called neurospheres, typically measure 100 - 200 m in diameter and are composed of approximately 10,000 - 100,000 cells. At this point, the neurospheres should be passaged to prevent the cell clusters from growing too large, which can lead to necrosis as a result of a lack of oxygen and nutrient exchange at the neurosphere center. To passage the cultures, neurospheres are individually, or as a population, mechanically or enzymatically dissociated into a single cell suspension and replated under the same conditions as the primary culture. NSCs and neural progenitor cells again begin to proliferate to form new cell clusters that are ready to be passaged approximately 5 - 7 days later. By repeating the above procedures for multiple passages, NSCs present in the culture will self-renew and produce a large number of progeny, resulting in a relatively consistent increase in total cell number over time. Neurospheres derived from embryonic mouse CNS tissue treated in this manner can be passaged for up to 10 weeks with no loss in their proliferative ability, resulting in a greater than 100- fold increase in total cell number. NSCs and neural progenitors can be induced to differentiate by removing the mitogens and plating either intact neurospheres or dissociated cells on an adhesive substrate, in the presence of a low serum-containing medium. After several days, virtually all of the NSCs and progeny will differentiate into the three main neural cell types found in the CNS: neurons, astrocytes and oligodendrocytes. While the culture medium, growth factor requirements and culture protocols may vary, the neurosphere culture system has been successfully used to isolate NSCs and progenitors from different regions of the embryonic and adult CNS of many species including mouse, rat and human.

Adherent monolayer culture: Alternatively, cells obtained from CNS tissues can be cultured as adherent cultures in a defined, serum-free medium supplemented with EGF and/or bFGF, in the presence of a substrate such as poly-L-ornithine, laminin, or fibronectin. When plated under these conditions, the neural stem and progenitor cells will attach to the substrate-coated cultureware, as opposed to each other, forming an adherent monolayer of cells, instead of neurospheres. The reported success of expanding NSCs in long-term adherent monolayer cultures is variable and may be due to differences in the substrates, serum-free media andgrowth factors used.17 Recently, protocols that have incorporated laminin as the substrate, along with an appropriate serum-free culture medium containing both EGF and bFGF have been able to support long-term cultures of neural precursors from mouse and human CNS tissues.30-32 These adherent cells proliferate and become confluent over the course of 5 - 10 days. To passage the cultures, cells are detached from the surface by enzymatic treatment and replated under the same conditions as the primary culture. It has been reported that NSCs cultured under adherent monolayer conditions undergo symmetric divisions in long-term culture.30,33 Similar to the neurosphere culture system, adherently cultured cells can be passaged multiple times and induced to differentiate into neurons, astrocytes and oligodendrocytes upon mitogen removal and exposure to a low serum-containing medium.

Several studies have suggested that culturing CNS cells in neurosphere cultures does not efficiently maintain NSCs and produces a heterogeneous cell population, whereas culturing cells under serum-free adherent culture conditions does maintain NSCs.17 While these reports did not directly compare neurosphere and adherent monolayer culture methods using the same medium, growth factors or extracellular matrix to evaluate NSC numbers, proliferation and differentiation potential, they emphasize that culture systems can influence the in vitro functional properties of NSCs and neural progenitors. It is important that in vitro methodologies for NSC research are designed with this caveat in mind, and with a clear understanding of what the methodologies are purported to measure.34-35

Immunomagnetic or immunofluorescent cell isolation strategies using antibodies directed against cell surface markers present on stem cells, progenitors and mature CNS cells have been applied to the study of NSCs. Similar to stem cells in other systems, the phenotype of CNS stem cells has not been completely determined. Expression, or lack of expression, of CD34, CD133 and CD45 antigens has been used as a strategy for the preliminary characterization of potential CNS stem cell subsets. A distinct subset of human fetal CNS cells with the phenotype CD133+ 5E12+ CD34- CD45- CD24-/lo has the ability to form neurospheres in culture, initiate secondary neurosphere formation, and differentiate into neurons and astrocytes.36 Using a similar approach, fluorescence-activated cell sorting (FACS)- based isolation of nestin+ PNA- CD24- cells from the adult mouse periventricular region enabled significant enrichment of NSCs(80% frequency in sorted population, representing a 100-fold increase from the unsorted population).37 However, the purity of the enriched NSC population was found to be lower when this strategy was reevaluated using the more rigorous Neural Colony-Forming Cell (NCFC) assay.38-39 NSC subsets detected at different stages of CNS development have been shown to express markers such as nestin, GFAP, CD15, Sox2, Musashi, CD133, EGFR, Pax6, FABP7 (BLBP) and GLAST40-45. However, none of these markers are uniquely expressed by NSCs; many are also expressed by neural progenitor cells and other nonneural cell types. Studies have demonstrated that stem cells in a variety of tissues, including bone marrow, skeletal muscle and fetal liver can be identified by their ability to efflux fluorescent dyes such as Hoechst 33342. Such a population, called the side population, or SP (based on its profile on a flow cytometer), has also been identified in both mouse primary CNS cells and cultured neurospheres.46 Other non-immunological methods have been used to identify populations of cells from normal and tumorigenic CNS tissues, based on some of the in vitro properties of stem cells, including FABP7 expression and high aldehyde dehydrogenase (ALDH) enzyme activity. ALDH-bright cells from embryonic rat and mouse CNS have been isolated and shown to have the ability to generate neurospheres, neurons, astrocytes and oligodendrocytes in vitro, as well as neurons in vivo, when transplanted into the adult mouse cerebral cortex.47-50 NeuroFluor CDr3 is a membrane-permeable fluorescent probe that binds to FABP7 and can be used to detect and isolate viable neural progenitor cells from multiple species.42-43

Multipotent neural stem-like cells, known as brain tumor stem cells (BTSCs) or cancer stem cells (CSCs), have been identified and isolated from different grades (low and high) and types of brain cancers, including gliomas and medulloblastomas.51-52 Similar to NSCs, these BTSCs exhibit self-renewal, high proliferative capacity and multi-lineage differentiation potential in vitro. They also initiate tumors that phenocopy the parent tumor in immunocompromised mice.53 No unique marker of BTSCs has been identified but recent work suggests that tumors contain a heterogenous population of cells with a subset of cells expressing the putative NSC marker CD133.53 CD133+ cells purified from primary tumor samples formed primary tumors, when injected into primary immunocompromised mice, and secondary tumors upon serial transplantation into secondary recipient mice.53 However, CD133 is also expressed by differentiated cells in different tissues and CD133- BTSCs can also initiate tumors in immunocompromised mice.54-55 Therefore, it remains to bedetermined if CD133 alone, or in combination with other markers, can be used to discriminate between tumor initiating cells and non-tumor initiating cells in different grades and types of brain tumors. Recently, FABP7 has gained traction as a CNS-specific marker of NSCs and BTSCs.42-43, 57

Both the neurosphere and adherent monolayer culture methods have been applied to the study of BTSCs. When culturing normal NSCs, the mitogen(s) EGF (and/or bFGF) are required to maintain NSC proliferation. However, there is some indication that these mitogens are not required when culturing BTSCs.57 Interestingly, the neurosphere assay may be a clinically relevant functional readout for the study of BTSCs, with emerging evidence suggesting that renewable neurosphere formation is a significant predictor of increased risk of patient death and rapid tumor progression in cultured human glioma samples.58-60 Furthermore, the adherent monolayer culture has been shown to enable pure populations of glioma-derived BTSCs to be expanded in vitro.61

Research in the field of NSC biology has made a significant leap forward over the past ~30 years. Contrary to the beliefs of the past century, the adult mammalian brain retains a small number of true NSCs located in specific CNS regions. The identification of CNS-resident NSCs and the discovery that adult somatic cells from mouse and human can be reprogrammed to a pluripotent state,62-68 and then directed to differentiate into neural cell types, has opened the door to new therapeutic avenues aimed at replacing lost or damaged CNS cells. This may include transplantation of neural progenitors derived from fetal or adult CNS tissue, or pluripotent stem cells. Recent research has shown that adult somatic cells can be directly reprogrammed to specific cell fates, such as neurons, using appropriate transcriptional factors, bypassing the need for an induced pluripotent stem cell intermediate.69 Astroglia from the early postnatal cerebracortex can be reprogrammed in vitro to neurons capable of action potential firing, by the forced expression of a single transcription factor, such as Pax6 or the pro-neural transcription factor neurogenin-2 (Neurog2).70 To develop cell therapies to treat CNS injuries and diseases, a greater understanding of the cellular and molecular properties of neural stem and progenitor cells is required. To facilitate this important research, STEMCELL Technologies has developed NeuroCult proliferation and differentiation kits for human, mouse and rat, including xenofree NeuroCult-XF. The NeuroCult NCFC Assay provides a simple and more accurate assay to enumerate NSCs compared to the neurosphere assay. These tools for NSC research are complemented by the NeuroCult SM Neuronal Culture Kits, specialized serum-free medium formulations for culturing primary neurons. Together, these reagents help to advance neuroscience research and assist in its transition from the experimental to the therapeutic phase.

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Neural Stem Cells - Stemcell Technologies

Spinal Cord Stem Cells Comments Off on Neural Stem Cells – Stemcell Technologies | October 2nd, 2019

06/06/2018

A stem cell treatment which is in primary stages of trials, has proved effective in treatment when using non-donor stem cells.

Spinal cord injuries can happen to anyone, the condition tends to be a result of a fall or accident, although it can also be an outcome of a brain injury. When the spinal cord is injured the pathway is practically closed. Nerve impulses cant get through, this has problematic symptoms such as; a person suffering paralysis, a loss of mobility and sensation.

Using stem cell therapy where the stem cells havent been donated mean they are more likely to be accepted by the patient when they are injected.

This new trial was published on the 9th of May 2018 inScience Translational Medicine, a team of international scientist led by the University of California San Diego School of Medicine successfully grafted stem cells back into a spinal cord without aggravating the immune system or reducing it in any way.

The stem cells injected in the trial were accepted and survived long term without causing a tumor. Researchers also found that the same cells showed a long-term survival when injected into an injured spinal cord.

Senior author Martin Marsala, MD, professor in the Department of Anesthesiology at UC San Diego School of Medicine and a member of the Sanford Consortium for Regenerative Medicine, said: The promise of iPSCs is huge, but so too have been the challenges. In this study, weve demonstrated an alternate approach,

We took skin cells, then induced them to becomeneural precursor cells(NPCs), destined to become nerve cells. Because they are syngeneicgenetically identical with the cell-graftthey are immunologically compatible. They grow and differentiate with no immunosuppression required.

Co-author Samuel Pfaff, PhD, professor and Howard Hughes Medical Institute Investigator at Salk Institute for Biological Studies, said: Using RNA sequencing and innovative bioinformatic method to deconvolute the RNAs species-of-origin, the research team demonstrated that iPSC-derived neural precursors safely acquire the genetic characteristics of mature CNS tissue.

In their study, researchers found that the stem cells survived and differentiated into neurons and supporting glial cells. The grafted stem cells were detected to be working and responsive seven months after transplantation.

Researchers, then grafted stem cells into similar tissues in the body that had severespinal cord injuries, this injection of stem cells was then followed by a transient four-week course of drugs that suppress the immune system. The stem cells then could work in the spinal cord and begin to allow movement.

Our current experiments are focusing on generation and testing of clinical grade human iPSCs, which is the ultimate source of cells to be used in future clinical trials for treatment of spinal cord and central nervous system injuries in a syngeneic or allogeneic setting, said Marsala.

Because long-term post-grafting periodsone to two yearsare required to achieve a full graftedcells-induced treatment effect, the elimination of immunosuppressive treatment will substantially increase our chances in achieving more robust functional improvement in spinal trauma patients receiving iPSC-derived NPCs.

In our current clinical cell-replacement trials, immunosuppression is required to achieve the survival of allogeneic cell grafts. The elimination of immunosuppression requirement by using syngeneic cell grafts would represent a major step forward said co-author Joseph Ciacci, MD, a neurosurgeon at UC San Diego Health and professor of surgery at UC San Diego School of Medicine.

The treatment is expected to go to the next stage of trials in the next few years, with the hope that this stem cell therapy can be used in modern medicine.

This research forms another significant step towards stem cell therapy and spinal cord injury. Yet the type of cell used is still in contention when it comes to human application. iPSC are undoubtedlyauseful research tool in the laboratory and as a result because of their pluripotency, many scientists continue to hopethat they can one day be used for therapeutic applications, including regenerative medicine in humans. This strategy continues to proveproblematic ashave been shown to produce lesions and tumors when injected or transplanted.

This type of research does however contribute to ongoing developments for the use of stem cells, where possible use of Adult Stem Cells, known not to be problematic as a result of tumors could be used.

We believe the best stem cells to use in emergingtreatmentswill be the patients own stem cells as this doesnt require a search for a suitable donor and in turn, eliminates chances of the transplanted cells being rejected.

If you want more information on how you can protect your childs future health by banking their cells, get in touch with our friendly team today or order your free information pack.

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Stem Cell Therapy May Be The Cure For Spinal Cord Injury ...

Spinal Cord Stem Cells Comments Off on Stem Cell Therapy May Be The Cure For Spinal Cord Injury … | September 14th, 2019

Open AccessReview

1

Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal

2

ICVS/3BsPT Government Associate Laboratory, Braga/Guimares, Portugal

*

Author to whom correspondence should be addressed.

Received: 12 March 2019 / Revised: 15 April 2019 / Accepted: 23 April 2019 / Published: 29 April 2019

No

MDPI and ACS Style

Pereira, I.M.; Marote, A.; Salgado, A.J.; Silva, N.A. Filling the Gap: Neural Stem Cells as A Promising Therapy for Spinal Cord Injury. Pharmaceuticals 2019, 12, 65.

Pereira IM, Marote A, Salgado AJ, Silva NA. Filling the Gap: Neural Stem Cells as A Promising Therapy for Spinal Cord Injury. Pharmaceuticals. 2019; 12(2):65.

Pereira, Ins M.; Marote, Ana; Salgado, Antnio J.; Silva, Nuno A. 2019. "Filling the Gap: Neural Stem Cells as A Promising Therapy for Spinal Cord Injury." Pharmaceuticals 12, no. 2: 65.

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Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

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Filling the Gap: Neural Stem Cells as A Promising Therapy ...

Spinal Cord Stem Cells Comments Off on Filling the Gap: Neural Stem Cells as A Promising Therapy … | June 3rd, 2019

JavaScript is disabled on your browser. Please enable JavaScript to use all the features on this page.Highlights

NSI-566 grafted injured spines in rats with near complete cavity-filling

The differentiation profile of grafted cells showed all three neural lineage cells

High-density human axonal sprouting was seen throughout the NSI-566 grafted region

NSI-566 transplanted in the spinal injury site of patients can be performed safely

We tested the feasibility and safety of human-spinal-cord-derived neural stem cell (NSI-566) transplantation for the treatment of chronic spinal cord injury (SCI). In this clinical trial, four subjects with T2T12 SCI received treatment consisting of removal of spinal instrumentation, laminectomy, and durotomy, followed by six midline bilateral stereotactic injections of NSI-566 cells. All subjects tolerated the procedure well and there have been no serious adverse events to date (1827months post-grafting). In two subjects, one to two levels of neurological improvement were detected using ISNCSCI motor and sensory scores. Our results support the safety of NSI-566 transplantation into the SCI site and earlysigns of potential efficacy in three of the subjects warrant further exploration of NSI-566 cells in dose escalation studies. Despite these encouraging secondary data, we emphasize that this safety trial lacks statistical power or a control group needed to evaluate functional changes resulting from cell grafting.

spinal cord injury

SCI

stem cell therapy

spinal surgery

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2018 Elsevier Inc.

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A First-in-Human, Phase I Study of Neural Stem Cell ...

Spinal Cord Stem Cells Comments Off on A First-in-Human, Phase I Study of Neural Stem Cell … | May 26th, 2019

"Stem Cell Cure Pvt. Ltd." is one of the most trusted and highlighted company in India which has expertise in providing best Stem Cell Services (for Blood disorders) in top most hospital of India for all major degenerative diseases. Our company is providing advanced medical treatment in India which applies in case of all other medical treatment fail to cure non-treatable diseases. We provide our services through some medical devices such as bone marrow aspiration concentrate (BMAC) kit, platelet rich plasma (PRP) kit, stem cell banking and stem cells services (isolated from bone marrow, placenta and adipose) for research/clinical trial purpose only.We are providing advanced medical treatment in India where all other medical treatment fail then this stem cell treatment apply to cure such non-treatable diseases.

It is the single channel that has comprehensive stem cell treatment and other medical treatment protocols and employs stem cells in different form as per the requirement of best suite on the basis of degenerative disease application. Stem cell therapy is helpful to treat many blood disorder such as thalassemia, sickle cell anemia, leukemia, aplastic anemia and other organ related disorder such as muscular dystrophy, spinal cord Injury, diabetes, chronic kidney disease (CKD), cerebral palsy, autism, optic nerve atrophy, retinitis pigmentosa, lung (COPD) disease and liver cirrhosis and our list of services doesn't end here.

"Stem Cell Cure" company is working with some India's top stem cell therapy centers, cord blood stem cell preservation banks and approved stem cell research labs to explore and share their unique stem cell solutions with our best services via coordinating of our clinician and researcher and solving every type of patient queries regarding stem cell therapy.

Our company is providing best medical treatment in India and also has expertization in stem cell therapy and for the needed patients in all those application which can treat by stem cell therapy. We have stem cells in different forms to make the better recovery of patient and refer the best stem cell solutions after the evaluation of patient case study by our experts. Our experts in this field work together with patients though the collaborative patient experience to give you greater peace of mind to develop clear evidence based path. We have highly experts in our team and our experts are strong in research and clinical research from both points of view.

Our mission is to provide best stem cell therapy at reasonable price not only in India but also throughout the whole world so that every needed patients can get best stem cell therapy to improve his life.

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Stem Cell Therapy in India - Stem Cell Treatment in Delhi ...

Spinal Cord Stem Cells Comments Off on Stem Cell Therapy in India – Stem Cell Treatment in Delhi … | May 20th, 2019

Abstract

Osteoarthritis (OA) is a chronic degenerative condition of the articular cartilage, which is the most common cause of disability in patients over age 65. Treatment options are limited towards alleviating symptomology.

Mesenchymal stem cells (MSC) are effective at treating osteoarthritis (OA) in animal models and clinical trials [1-6]. Mechanisms of therapeutic activity appear to be associated with regenerative and anti-inflammatory factors produced by MSC [7, 8]. On the one hand, MSC produce soluble factors that are antioxidant [9], antifibrotic [10], and stimulate endogenous chondrogenic progenitors [11], on the other hand MSC directly can differentiate into cartilage tissue [12].

The proposed study will involve intra-articular injection of umbilical cord tissue mesenchymal stem cells (UC-MSC) into joints of 20 patients with grade 2-4 radiographic OA severity and intravenously in 20 patients with grade 2-4 radiographic OA severity. The primary endpoint will be safety and feasibility as assessed by lack of treatment associated adverse events. The secondary endpoint will be improvements in joint function as assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Patients will be examined at baseline and 3 and 12 months after treatment.

This, study will provide support for double-blind placebo controlled investigations. The potential of using UC-MSC for this debilitating condition will open the door for future investigations in other inflammatory conditions if results demonstrate safety and feasibility of this approach.

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Human Umbilical Cord Stem Cells for Osteoarthritis ...

Spinal Cord Stem Cells Comments Off on Human Umbilical Cord Stem Cells for Osteoarthritis … | April 22nd, 2019

Statistics indicate that approximately 17,500 people suffer spinal cord injuries each year. Although these injuries can impact anyone, they are most commonly seen in younger men, primarily because these injuries are often driven by lifestyle choices that people may make. Yet, despite efforts to more effectively treat these spinal cord injuries and restore full quality of life, traditional medical treatments have largely been unsuccessful.

Due to this fact, medical professionals have increasingly turned their attention to stem cells and how these stem cells could be used to treat spinal cord injuries.

In short, there is no way to reverse damage to the spinal cord that doesnt include replacing the old cells, like with stem cells. However, there are some treatment options available as to prevent the injury becoming worse, especially immediately during or after the injury event. With any luck, some patients can return to an active and normal life through these means without having to resort to stem cells, which is still a clinical and expensive treatment.

Most of what can be done for a spinal cord injury is at the scene. These require the patient to remain motionless in order to prevent shock. Immobilizing the neck and spinal cord can help reduce further injury and complications, not to mention maintaining steady breathing. Surgery is often necessary for this type of injury. Some medication, particularly methylprednisolone, can be used, but the side effects of blood clots and illness usually outweigh the benefits.

In the long run, doctors make a priority to prevent problems with other parts of the body as a result of spinal cord injuries. Blood clots, respiratory infections, pressure ulcers and other issues have been known to arise.

Otherwise, rehabilitation is almost always recommended to rebuild muscle strength while in the early stages of recovery. Education on how to prevent further complications in day-to-day life is also given to patients with these types of injuries, along with learning new skills to help through their new situation.

With treatment for spinal cord injuries being severely limited, there is little wonder why doctors and researchers have turned to the idea of using stem cells to rebuild and replace damaged cells. However, these stem cells cant just be injected in any traditional sense. They need to be placed accurately in an environment where they can grow. This is where 3D printing comes in.

Recognizing the fact that traditional treatment methods have not been able to fully improve patients quality of life, medical professionals are shifting their attention to exploring stem cells and how stem cells can improve functioning for individuals with spinal cord injuries. The pioneering study in this sphere came out of the University of California San Diegos School of Medicine and Institute of Engineering.

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3D Printing Stem Cells for Treating Spinal Cord Injuries

Spinal Cord Stem Cells Comments Off on 3D Printing Stem Cells for Treating Spinal Cord Injuries | April 18th, 2019

Together, the brain and spinal cord form the central nervous system. This complex system is part of everything we do. It controls the things we choose to do -- like walk and talk -- and the things our body does automatically -- like breathe and digest food. The central nervous system is also involved with our senses -- seeing, hearing, touching, tasting, and smelling -- as well as our emotions, thoughts, and memory.

The brain is a soft, spongy mass of nerve cells and supportive tissue. It has three major parts: the cerebrum, the cerebellum, and the brain stem. The parts work together, but each has special functions.

The cerebrum, the largest part of the brain, fills most of the upper skull. It has two halves called the left and right cerebral hemispheres. The cerebrum uses information from our senses to tell us what's going on around us and tells our body how to respond. The right hemisphere controls the muscles on the left side of the body, and the left hemisphere controls the muscles on the right side of the body. This part of the brain also controls speech and emotions as well as reading, thinking, and learning.

The cerebellum, under the cerebrum at the back of the brain, controls balance and complex actions like walking and talking.

The brain stem connects the brain with the spinal cord. It controls hunger and thirst and some of the most basic body functions, such as body temperature, blood pressure, and breathing.

The brain is protected by the bones of the skull and by a covering of three thin membranes called meninges. The brain is also cushioned and protected by cerebrospinal fluid. This watery fluid is produced by special cells in the four hollow spaces in the brain, called ventricles. It flows through the ventricles and in spaces between the meninges. Cerebrospinal fluid also brings nutrients from the blood to the brain and removes waste products from the brain.

The spinal cord is made up of bundles of nerve fibers. It runs down from the brain through a canal in the center of the bones of the spine. These bones protect the spinal cord. Like the brain, the spinal cord is covered by the meninges and cushioned by cerebrospinal fluid.

Spinal nerves connect the brain with the nerves in most parts of the body. Other nerves go directly from the brain to the eyes, ears, and other parts of the head. This network of nerves carries messages back and forth between the brain and the rest of the body

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About The Brain and Spinal Cord | Neurosurgery ...

Spinal Cord Stem Cells Comments Off on About The Brain and Spinal Cord | Neurosurgery … | March 16th, 2019

Scientists in Japan now have permission to inject 'reprogrammed' stem cells into people with spinal-cord injuries.

An upcoming trial will mark the first time that induced pluripotent stem (iPS) cells have been used to treat spinal-cord injuries, after a committee at Japans health ministry approved the study on 18 February. IPS cells are created by inducing cells from body tissue to revert to an embryonic-like state, from which they can develop into other cell types.

Hideyuki Okano, a stem-cell scientist at Keio University in Tokyo, will coax donor iPS cells into becoming neural precursor cells, which can develop into neurons and glial cells. His team will then inject two million of the precursor cells per patient into the site of spinal injury around 24 weeks after the injury occurs. .

Okano has demonstrated that the procedure can regenerate neurons in monkeys with injured spinal cords and increase their mobility1.

Okanos team will carry out the experimental therapy in four people, monitoring them to ensure it is safe and effective before deciding whether to start a larger clinical trial with more participants. The first patient is expected to be treated in the second half of this year.

IPS cells have been used in a handful of other clinical applications, including to treat age-related macular degeneration in 2014 and 2017, and Parkinsons disease in 2018.

A clinical trial in the United States is also testing a treatment for spinal-cord injuries using embryonic stem cells. The study has so far only led to minor improvements in a few patients, and has yet to demonstrate that it works in a controlled trial.

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Reprogrammed stem cells to treat spinal-cord injuries ...

Spinal Cord Stem Cells Comments Off on Reprogrammed stem cells to treat spinal-cord injuries … | February 24th, 2019

Japan trial to treat spinal cord injuries with stem cells

TOKYO: A team of Japanese researchers will carry out an unprecedented trial using a kind of stem cell to try to treat debilitating spinal cord injuries, the specialists said on Monday.

The team at Tokyos Keio University has received government approval for a trial using so-called induced Pluripotent Stem (iPS) cells, which have the potential to develop into any cell in the body, to treat patients with serious spinal cord injuries.

The trial, expected to begin later this year, will initially focus on four patients who suffered their injuries just 14 to 28 days beforehand, the university said. The team will transplant two million iPS cells into the spines of the patients, who will then go through rehabilitation and be monitored for a year.

The strict limitations on the number of participants is necessary because the process is an "unprecedented, world first clinical trial", the university added. "Its been 20 years since I started researching cell treatment. Finally we can start a clinical trial," Hideyuki Okano, a professor of physiology, said at a press conference.

"We want to do our best to establish safety and provide the treatment to patients," he added. The study will be carried out on patients aged 18 or older who have completely lost their motor and sensory functions.

There are more than 100,000 patients in Japan who are paralysed due to spinal cord injuries but there is no effective treatment. The primary purpose of the trial is to confirm the safety of the transplanted cells and the method of the transplant, the researchers said.

The research team hopes to test the efficacy and safety of the treatment for chronic injuries as well in the future if they can confirm the safety of the technique through the clinical trial. The announcement comes after researchers in Kyoto said in November they had transplanted iPS cells into the brain of a patient in a bid to cure Parkinsons disease. The man was stable after the operation and he will be monitored for two years.

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Japan trial to treat spinal cord injuries with stem cells ...

Spinal Cord Stem Cells Comments Off on Japan trial to treat spinal cord injuries with stem cells … | February 20th, 2019

You may have heard of stem cells in the news and that they are being used in medical research. This can be a controversial topic for many, but the fact is that the research is happening in specialties across the medical industry. Lets start with the basics to clarify how stem cells are being used in research for spinal cord injuries.

This is the bundle of nerve fibers that transmits information between the brain and rest of the body, protected by the hard vertebrae spinal column. Made up of millions of nerve cells, when connected to the brain, this forms the central nervous system. Injury to the spinal cord can cause paralysis or even death, and there is currently no effective treatment.

Following an injury, the nerve cells and motor axons, which make up the spinal cord, are crushed and torn, and the insulating sheath around the axons begins to die. Any exposed axons begin to degenerate, which means the neuron connection is disrupted, and the flow of information between thebrain and the spinal cord is subsequently blocked.

When this happens, the body is unable to replace lost cells from a spinal cord injury. As a result, their function becomes permanently impaired, leading to severe movement and sensation disability which doctors measure on various scales, including the American Spinal Injury Association Impairment Scale (AIS).

Although the research is still in its infancy, professionals believe stem cells are an ideal answer to contribute to spinal cord treatment and repair. The two main characteristics of stem cells, which make them so well-suited for this use, is

Stem cells, come from two main sources- embryonic stem cells from an embryo and somatic stem cells found throughout the body.

Studies in animals demonstrated that transplantation of stem cells contributed to the repair of spinal cord material. It did so in various ways, and these included the replacement of dead nerve cells; the generation of new cells to re-form the aforementioned insulating sheath around the axons, to stimulate the regrowth of damaged axons. It also acted to protect cells at the site of the injury from any further damage.

In prior testing situations, stem cells have been removed from brain tissue, nasal cavity lining, and tooth pulp for applications. This has only ever resulted in partial recovery of function, however, and remains in experimental stages.

There is controversy over this type of treatment at the moment; due to the fact stem cells need further research into how they behave and how they could work in a form of treatment. Stem cell behavior is directed by chemical signals, some of which are internal, and others of which are external and depend on the environment they find themselves in. These chemical signals would need to be created in the spinal cord environment in order to encourage relative growth and development.

Although stem cell treatment continues to be in testing stages, it is still a possible solution for repairing spinal cord injuries at some point in the future.

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What Do Stem Cells Have to Do with a Spinal Cord Injury?

Spinal Cord Stem Cells Comments Off on What Do Stem Cells Have to Do with a Spinal Cord Injury? | February 5th, 2019

At Spinal Cord, were excited to share that researchers at the University of California, San Diego successfully created spinal cord neural stem cells (NSCs) that could have clinical applications in spinal cord injury and disorder treatments.

The spinal cord injury research, conducted by postdoctoral scholar Hiromi Kumamaru and Professor of Neuroscience and Director of the UCSD Translational Neuroscience Institute Mark Tuszynski, grafted the cultured cells into the spinal cords of rats with spinal cord injuries (SCIs).

Kumamaru says about the spinal cord injury research:

In grafts, these cells could be found throughout the spinal cord, dorsal to ventral. They promoted regeneration after spinal cord injury in adult rats, including corticospinal axons, which are extremely important in human voluntary motor function. In rats, they supported functional recovery.

These diverse cells are derived from immature self-replicating human stem cells known as human pluripotent stem cells (hPSCs), which morph into different types of stem cells that could disperse throughout the spinal cord. According to the researchers, these pluripotent cells could serve as a scalable source of replacement cells for individuals with spinal cord injuries.

In the Universitys press release, Tuszynski says that the new cells could serve as source cells for human clinical trials in three to five years. First, however, it first needs to be determined whether the cells are safe over long-time periods via studies on rodents and non-human primates and that the results are replicable.

According to the Universitys press release on the new stem cell research:

The achievement, described in the August 6 online issue of Nature Methods, advances not only basic research like biomedical applications of in vitro disease modeling, but may constitute an improved, clinically translatable cell source for replacement strategies in spinal cord injuries and disorders.

The hope is that the cultured spinal cord neural stem cells from this stem cell research will benefit people with other spinal cord dysfunction disorders via modeling and drug screening. According to UCSD, such disorders would include amyotrophic lateral sclerosis, progressive muscular atrophy, hereditary spastic paraplegia and spinocerebellar ataxia, a group of genetic disorders characterized by progressive discoordination of gait, hands and eye movement.

Although significant research has been done to explore the potential use of hPSC stem cells in creating new cells to repair diseased or damaged spinal cords, historically, progress has been slow and limited.

It is one of the goals of the Spinal Cord team to help keep you and your family informed about the newest medical advances in spinal cord injury research. We recently shared about exciting advances in gene therapy research that helped to restore hand function in rats with SCIs, as well as the use of olfactory ensheathing cells (cells from the bodys system that enables you to perceive smells) to trigger spinal cord nerve regeneration.

Please be sure to subscribe to our blog to get the latest updates on stem cell and other spinal cord injury research.

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Spinal Cord Injury Research Advances with New Stem Cells

Spinal Cord Stem Cells Comments Off on Spinal Cord Injury Research Advances with New Stem Cells | February 4th, 2019

Spinal Cord Injuries Are Not JustCaused by Trauma

When you think of spinal cord injury (SCI), traumatic events like a serious car accident may come to mind. While its true that car accidents are the leading cause of traumatic SCI, you may be surprised that non-traumatic diseasessuch as a spinal tumorcan also cause SCI.

SCI involves damage to the spinal cord that temporarily or permanently changes how it functions. SCI is divided into 2 categories: traumatic or non-traumatic. Even if the cause of SCI is non-traumatic, that doesnt lessen its impact or severitythe aftermath of SCI can have devastating effects on a persons life.Falls are the second most common cause of traumatic spinal cord injury. Photo Source: 123RF.com.Traumatic Spinal Cord Injury

Traumatic SCI occurs more often in men than womennearly 80% of cases affect men. People of all ages may experience SCI, but certain activities tend to affect different age groups more. For example, high-impact events like car accidents and sports injuries tend to occur more often in younger people. On the other hand, traumatic SCI caused by a fall is more common in adults over age 60.

Regardless of the cause, traumatic SCI occurs most frequently in the cervical spine (about 60% of cases involve the neck), followed by thoracic spine (32% involve the mid-back). Only 9% of cases occur in the lumbosacral spine, or low back and tailbone.

Understanding the Traumatic Spinal Cord Injury CascadeA traumatic SCI doesnt simply damage your spinal cord at the point of initial impact. In traumatic SCI, the primary injury (that is, the initial traumatic event that caused the SCI) may damage cells and dislocate your spinal vertebrae, which causes spinal cord compression. The primary injury also triggers a complex secondary injury cascade, which causes a series of biological changes that may occur weeks and months after the initial injury.

During the secondary injury cascade, the following processes occur:

This cascade changes the spinal cords structure and how it normally operates. Ultimately, this secondary injury cascade may interfere with the spinal cords ability to recover itself. This means a person with traumatic SCI may experience permanent nerve pain and dysfunction because of their injury.

Non-traumatic Spinal Cord InjuryTraumatic events arent the only causes of spinal cord damageSCI can also be caused by non-traumatic diseases in the spine. Spinal tumors are the leading cause of non-traumatic SCI, but infections and degenerative disc disease can also damage your spinal cord.

Though most people connect traumatic events to SCI, non-traumatic causes of SCI are a much more likely cause. To highlight just how common non-traumatic cases are versus their traumatic counterparts, consider the incidence of traumatic SCI in North America: 39 cases per million people. On the other hand, the incidence of non-traumatic SCI is 1,227 cases per million people for Canada alone (data for the rest of North America is not available).

A Healthy Research Outlook to Improve Spinal Cord Injury OutcomesOver the past 30 years, spine researchers have made great strides in developing successful protective and regenerative therapies to improve the health of the spinal cord and the survival rate of people with SCIbut the work is far from over. Current studies and clinical trials are examining innovative medical, surgical and cell-based treatments to further the medical communitys understanding of SCI, which will improve the quality of life and preserve a brighter future for people who experience these injuries.

Suggested Additional ReadingA special issue of the Global Spine Journal set forth guidelines for the Management of Degenerative Myelopathy and Acute Spinal Cord Injury, which is summarized on SpineUniverse in Summary of the Clinical Practice Guidelines for the Management of Degenerative Cervical Myelopathy and Traumatic Spinal Cord Injury.

Sources:Ahuja CS, Wilson JR, Nori S, et al. Traumatic spinal cord injury. Nature Reviews Disease Primers. 3, 17018. https://www.nature.com/articles/nrdp201718. Accessed January 10, 2018.

Spinal Cord Injury. Facts and figures at a glance. National SCI Statistical Center (NSCI SC). 2017. https://www.nscisc.uab.edu/. Accessed January 10, 2018.

Updated on: 01/27/19

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Spinal Cord Injury Center - Treatments, Research ...

Spinal Cord Stem Cells Comments Off on Spinal Cord Injury Center – Treatments, Research … | February 2nd, 2019

The C3, C4, and C5 vertebrae form the midsection of the cervical spine, near the base of the neck. Injuries to the nerves and tissue relating to the cervical regionare the most severe of all spinal cord injuries because the higher up in the spine an injury occurs, the more damage that is caused to the central nervous system. Depending on the how severe the damage to the spinal cord is, the injury may be noted as complete or incomplete.

The C2 - C3 junction of the spinal column is important, as this is where flexion and extension occur (flexion is the movement of the chin toward the chest and extension is the backward movement of the head). Patients with spinal cord damage at the C3 level will have limited mobility in both their flexion and extension.

Symptoms of a spinal cord injury corresponding toC3 vertebrae include:

The portion of the spinal cord which relatesto the C4 vertebra directly affects the diaphragm. Patients with C4 spinal cord injuries typically need 24 hour-a-day support to breathe and maintain oxygen levels.

Symptoms of a spinal cord injury corresponding toC4 vertebrae include:

Damage to the spinal cord at the C5 vertebra affects the vocal cords, biceps, and deltoid muscles in the upper arms. Unlike some of the higher cervical injuries, a patient with a C5 spinal cord injury will likely be able to breath and speak on their own.

Symptoms of a spinal cord injury corresponding to C5 vertebrae include:

The most common causes of cervical spinal cord injuries are:

Unfortunately, there is no treatment which will completely reverse the damage frominjuries to the spinal cord at the C3 - C5 levels. Medical care is focused on preventingfurther damage to the spinal cord and utilization of remaining function.

Current treatments available for patients are:

It is an unfortunate truth that there are not many options to date to completely recover from a cervical spinal cord injury. Medical researchers are continuously looking into new drug therapies to help regain sensory and motor function. The use of stem cells is seen more and more in research as these cells are specialized enough to possibly regenerate damaged spinal cord tissues. Lab study results show greater sensory and motor function in those patients treated with stem cells for spinal cord damage.

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C3, C4, & C5 Vertebrae Spinal Cord Injury | SpinalCord.com

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Causes of spinal cord disorders include injuries, infections, a blocked blood supply, and compression by a fractured bone or a tumor.

Typically, muscles are weak or paralyzed, sensation is abnormal or lost, and controlling bladder and bowel function may be difficult.

Doctors base the diagnosis on symptoms and results of a physical examination and imaging tests, such as magnetic resonance imaging.

The condition causing the spinal cord disorder is corrected if possible.

Often, rehabilitation is needed to recover as much function as possible.

The spinal cord is the main pathway of communication between the brain and the rest of the body. It is a long, fragile, tubelike structure that extends downward from the base of the brain. The cord is protected by the back bones (vertebrae) of the spine (spinal column). The vertebrae are separated and cushioned by disks made of cartilage.

The spine (spinal column) contains the spinal cord, which is divided into four sections:

Each section is referred to by a letter (C, T, L, or S).

The vertebrae in each section of the spine are numbered beginning at the top. For example, the first vertebra in the cervical spine is labeled C1, the second in the cervical spine is C2, the second in the thoracic spine is T2, the fourth in the lumbar spine is L4, and so forth. These labels are also used to identify specific locations (called levels) in the spinal cord.

Nerves run from a specific level of the spinal cord to a specific area of the body. By noting where a person has weakness, paralysis, sensory loss, or other loss of function, a neurologist can determine where the spinal cord is damaged.

The spine is divided into four sections, and each section is referred to by a letter.

Within each section of the spine, the vertebrae are numbered beginning at the top. These labels (letter plus a number) are used to indicate locations (levels) in the spinal cord.

Along the length of the spinal cord, 31 pairs of spinal nerves emerge through spaces between the vertebrae. Each spinal nerve runs from a specific vertebra in the spinal cord to a specific area of the body. Based on this fact, the skins surface has been divided into areas called dermatomes. A dermatome is an area of skin whose sensory nerves all come from a single spinal nerve root. Loss of sensation in a particular dermatome enables doctors to locate where the spinal cord is damaged.

The surface of the skin is divided into specific areas, called dermatomes. A dermatome is an area of skin whose sensory nerves all come from a single spinal nerve root. (Sensory nerves carry information about such things as touch, pain, temperature, and vibration from the skin to the spinal cord.)

Spinal roots come in pairsone of each pair on each side of the body. There are 31 pairs:

There are 8 pairs of sensory nerve roots for the 7 cervical vertebrae.

Each of the 12 thoracic, 5 lumbar, and 5 sacral vertebrae has one pair of spinal nerve roots.

In addition, at the end of the spinal cord, there is a pair of coccygeal nerve roots, which supply a small area of the skin around the tailbone (coccyx).

There are dermatomes for each of these nerve roots.

Sensory information from a specific dermatome is carried by sensory nerve fibers to the spinal nerve root of a specific vertebra. For example, sensory information from a strip of skin along the back of the thigh is carried by sensory nerve fibers to the 2nd sacral vertebra (S2) nerve root.

A spinal nerve has two nerve roots (a motor root and a sensory root). The only exception is the first spinal nerve, which has no sensory root.

Motor root: The root in the front (the motor or anterior root) contains nerve fibers that carry impulses (signals) from the spinal cord to muscles to stimulate muscle movement (contraction).

Sensory root: The root in the back (the sensory or posterior root) contains nerve fibers that carry sensory information about touch, position, pain, and temperature from the body to the spinal cord.

The spinal cord ends in the lower back (around L1 or L2), but the lower spinal nerve roots continue, forming a bundle that resembles a horses tail (called the cauda equina).

The spinal cord is highly organized (see figure How the Spine Is Organized). The center of the cord consists of gray matter shaped like a butterfly:

The front "wings" (anterior or motor horns) contain nerve cells that carry signals from the brain or spinal cord through the motor root to muscles.

The back (posterior or sensory) horns contain nerve cells that receive signals about pain, temperature, and other sensory information through the sensory root from nerve cells outside the spinal cord.

The outer part of the spinal cord consists of white matter that contains pathways of nerve fibers (called tracts or columns). Each tract carries a specific type of nerve signal either going to the brain (ascending tracts) or from the brain (descending tracts).

Spinal nerves carry nerve impulses to and from the spinal cord through two nerve roots:

Motor (anterior) root: Located toward the front, this root carries impulses from the spinal cord to muscles to stimulate muscle movement.

Sensory (posterior) root: Located toward the back, this root carries sensory information about touch, position, pain, and temperature from the body to the spinal cord.

In the center of the spinal cord, a butterfly-shaped area of gray matter helps relay impulses to and from spinal nerves. Its "wings" are called horns.

Motor (anterior) horns: These horns contain nerve cells that carry signals from the brain or spinal cord through the motor root to muscles.

Posterior (sensory) horns: These horns contain nerve cells that receive signals about pain, temperature, and other sensory information through the sensory root from nerve cells outside the spinal cord.

Impulses travel up (to the brain) or down (from the brain) the spinal cord through distinct pathways (tracts). Each tract carries a different type of nerve signal either going to or from the brain. The following are examples:

Lateral spinothalamic tract: Signals about pain and temperature, received by the sensory horn, travel through this tract to the brain.

Dorsal columns: Signals about the position of the arms and legs travel through the dorsal columns to the brain.

Corticospinal tracts: Signals to move a muscle travel from the brain through these tracts to the motor horn, which routes them to the muscle.

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Overview of Spinal Cord Disorders - Brain, Spinal Cord ...

Spinal Cord Stem Cells Comments Off on Overview of Spinal Cord Disorders – Brain, Spinal Cord … | January 29th, 2019

The spinal cord is an elongated cylindrical structure, about 45 cm (18 inches) long, that extends from the medulla oblongata to a level between the first and second lumbar vertebrae of the backbone. The terminal part of the spinal cord is called the conus medullaris. The spinal cord is composed of long tracts of myelinated nerve fibres (known as white matter) arranged around the periphery of a symmetrical butterfly-shaped cellular matrix of gray matter. The gray matter contains cell bodies, unmyelinated motor neuron fibres, and interneurons connecting either the two sides of the cord or the dorsal and ventral ganglia. Many interneurons have short axons distributed locally, but some have axons that extend for several spinal segments. Some interneurons may modulate or change the character of signals, while others play key roles in transmission and in patterned reflexes. The gray matter forms three pairs of horns throughout most of the spinal cord: (1) the dorsal horns, composed of sensory neurons, (2) the lateral horns, well defined in thoracic segments and composed of visceral neurons, and (3) the ventral horns, composed of motor neurons. The white matter forming the ascending and descending spinal tracts is grouped in three paired funiculi, or sectors: the dorsal or posterior funiculi, lying between the dorsal horns; the lateral funiculi, lying on each side of the spinal cord between the dorsal-root entry zones and the emergence of the ventral nerve roots; and the ventral funiculi, lying between the ventral median sulcus and each ventral-root zone.

Associated with local regions of the spinal cord and imposing on it an external segmentation are 31 pairs of spinal nerves, each of which receives and furnishes one dorsal and one ventral root. On this basis the spinal cord is divided into the following segments: 8 cervical (C), 12 thoracic (T), 5 lumbar (L), 5 sacral (S), and 1 coccygeal (Coc). Spinal nerve roots emerge via intervertebral foramina; lumbar and sacral spinal roots, descending for some distance within the subarachnoid space before reaching the appropriate foramina, produce a group of nerve roots at the conus medullaris known as the cauda equina. Two enlargements of the spinal cord are evident: (1) a cervical enlargement (C5 through T1), which provides innervation for the upper extremities, and (2) a lumbosacral enlargement (L1 through S2), which innervates the lower extremities. (The spinal nerves and the area that they innervate are described in the section The peripheral nervous system: Spinal nerves.)

The gray matter of the spinal cord is composed of nine distinct cellular layers, or laminae, traditionally indicated by Roman numerals. Laminae I to V, forming the dorsal horns, receive sensory input. Lamina VII forms the intermediate zone at the base of all horns. Lamina IX is composed of clusters of large alpha motor neurons, which innervate striated muscle, and small gamma motor neurons, which innervate contractile elements of the muscle spindle. Axons of both alpha and gamma motor neurons emerge via the ventral roots. Laminae VII and VIII have variable configurations, and lamina VI is present only in the cervical and lumbosacral enlargements. In addition, cells surrounding the central canal of the spinal cord form an area often referred to as lamina X.

All primary sensory neurons that enter the spinal cord originate in ganglia that are located in openings in the vertebral column called the intervertebral foramina. Peripheral processes of the nerve cells in these ganglia convey sensation from various receptors, and central processes of the same cells enter the spinal cord as bundles of nerve filaments. Fibres conveying specific forms of sensation follow separate pathways. Impulses involved with pain and noxious stimuli largely end in laminae I and II, while impulses associated with tactile sense end in lamina IV or on processes of cells in that lamina. Signals from stretch receptors (i.e., muscle spindles and tendon organs) end in parts of laminae V, VI, and VII; collaterals of these fibres associated with the stretch reflex project into lamina IX.

Virtually all parts of the spinal gray matter contain interneurons, which connect various cell groups. Many interneurons have short axons distributed locally, but some have axons that extend for several spinal segments. Some interneurons may modulate or change the character of signals, while others play key roles in transmission and in patterned reflexes.

Sensory tracts ascending in the white matter of the spinal cord arise either from cells of spinal ganglia or from intrinsic neurons within the gray matter that receive primary sensory input.

The largest ascending tracts, the fasciculi gracilis and cuneatus, arise from spinal ganglion cells and ascend in the dorsal funiculus to the medulla oblongata. The fasciculus gracilis receives fibres from ganglia below thoracic 6, while spinal ganglia from higher segments of the spinal cord project fibres into the fasciculus cuneatus. The fasciculi terminate upon the nuclei gracilis and cuneatus, large nuclear masses in the medulla. Cells of these nuclei give rise to fibres that cross completely and form the medial lemniscus; the medial lemniscus in turn projects to the ventrobasal nuclear complex of the thalamus. By this pathway, the medial lemniscal system conveys signals associated with tactile, pressure, and kinesthetic (or positional) sense to sensory areas of the cerebral cortex.

Fibres concerned with pain, thermal sense, and light touch enter the lateral-root entry zone and then ascend or descend near the periphery of the spinal cord before entering superficial laminae of the dorsal hornlargely parts of laminae I, IV, and V. Cells in these laminae then give rise to fibres of the two spinothalamic tracts. Those fibres crossing in the ventral white commissure (ventral to the central canal) form the lateral spinothalamic tract, which, ascending in the ventral part of the lateral funiculus, conveys signals related to pain and thermal sense. The anterior spinothalamic tract arises from fibres that cross the midline in the same fashion but ascend more anteriorly in the spinal cord; these fibres convey impulses related to light touch. At medullary levels the two spinothalamic tracts merge and cannot be distinguished as separate entities. Many of the fibres, or collaterals, of the spinothalamic tracts terminate upon cell groups in the reticular formation, while the principal tracts convey sensory impulses to relay nuclei in the thalamus.

Impulses from stretch receptors are carried by fibres that synapse upon cells in deep laminae of the dorsal horn or in lamina VII. The posterior spinocerebellar tract arises from the dorsal nucleus of Clarke and ascends peripherally in the dorsal part of the lateral funiculus. The anterior spinocerebellar tract ascends on the ventral margin of the lateral funiculus. Both tracts transmit signals to portions of the anterior lobe of the cerebellum and are involved in mechanisms that automatically regulate muscle tone without reaching consciousness.

Tracts descending to the spinal cord are involved with voluntary motor function, muscle tone, reflexes and equilibrium, visceral innervation, and modulation of ascending sensory signals. The largest, the corticospinal tract, originates in broad regions of the cerebral cortex. Smaller descending tracts, which include the rubrospinal tract, the vestibulospinal tract, and the reticulospinal tract, originate in nuclei in the midbrain, pons, and medulla oblongata. Most of these brainstem nuclei themselves receive input from the cerebral cortex, the cerebellar cortex, deep nuclei of the cerebellum, or some combination of these.

In addition, autonomic tracts, which descend from various nuclei in the brainstem to preganglionic sympathetic and parasympathetic neurons in the spinal cord, constitute a vital link between the centres that regulate visceral functions and the nerve cells that actually effect changes.

The corticospinal tract originates from pyramid-shaped cells in the premotor, primary motor, and primary sensory cortex and is involved in skilled voluntary activity. Containing about one million fibres, it forms a significant part of the posterior limb of the internal capsule and is a major constituent of the crus cerebri in the midbrain. As the fibres emerge from the pons, they form compact bundles on the ventral surface of the medulla, known as the medullary pyramids. In the lower medulla about 90 percent of the fibres of the corticospinal tract decussate and descend in the dorsolateral funiculus of the spinal cord. Of the fibres that do not cross in the medulla, approximately 8 percent cross in cervical spinal segments. As the tract descends, fibres and collaterals branch off at all segmental levels, synapsing upon interneurons in lamina VII and upon motor neurons in lamina IX. Approximately 50 percent of the corticospinal fibres terminate within cervical segments.

At birth, few of the fibres of the corticospinal tract are myelinated; myelination takes place during the first year after birth, along with the acquisition of motor skills. Because the tract passes through, or close to, nearly every major division of the neuraxis, it is vulnerable to vascular and other kinds of lesions. A relatively small lesion in the posterior limb of the internal capsule, for example, may result in contralateral hemiparesis, which is characterized by weakness, spasticity, greatly increased deep tendon reflexes, and certain abnormal reflexes.

The rubrospinal tract arises from cells in the caudal part of the red nucleus, an encapsulated cell group in the midbrain tegmentum. Fibres of this tract decussate at midbrain levels, descend in the lateral funiculus of the spinal cord (overlapping ventral parts of the corticospinal tract), enter the spinal gray matter, and terminate on interneurons in lamina VII. Through these crossed rubrospinal projections, the red nucleus exerts a facilitating influence on flexor alpha motor neurons and a reciprocal inhibiting influence on extensor alpha motor neurons. Because cells of the red nucleus receive input from the motor cortex (via corticorubral projections) and from globose and emboliform nuclei of the cerebellum (via the superior cerebellar peduncle), the rubrospinal tract effectively brings flexor muscle tone under the control of these two regions of the brain.

The vestibulospinal tract originates from cells of the lateral vestibular nucleus, which lies in the floor of the fourth ventricle. Fibres of this tract descend the length of the spinal cord in the ventral and lateral funiculi without crossing, enter laminae VIII and IX of the anterior horn, and terminate upon both alpha and gamma motor neurons, which innervate ordinary muscle fibres and fibres of the muscle spindle (see below Functions of the human nervous system: Movement). Cells of the lateral vestibular nucleus receive facilitating impulses from labyrinthine receptors in the utricle of the inner ear and from fastigial nuclei in the cerebellum. In addition, inhibitory influences upon these cells are conveyed by direct projections from Purkinje cells in the anterior lobe of the cerebellum. Thus, the vestibulospinal tract mediates the influences of the vestibular end organ and the cerebellum upon extensor muscle tone.

A smaller number of vestibular projections, originating from the medial and inferior vestibular nuclei, descend ipsilaterally in the medial longitudinal fasciculus only to cervical levels. These fibres exert excitatory and inhibitory effects upon cervical motor neurons.

The reticulospinal tracts arise from relatively large but restricted regions of the reticular formation of the pons and medulla oblongatathe same cells that project ascending processes to intralaminar thalamic nuclei and are important in the maintenance of alertness and the conscious state. The pontine reticulospinal tract arises from groups of cells in the pontine reticular formation, descends ipsilaterally as the largest component of the medial longitudinal fasciculus, and terminates among cells in laminae VII and VIII. Fibres of this tract exert facilitating influences upon voluntary movements, muscle tone, and a variety of spinal reflexes. The medullary reticulospinal tract, originating from reticular neurons on both sides of the median raphe, descends in the ventral part of the lateral funiculus and terminates at all spinal levels upon cells in laminae VII and IX. The medullary reticulospinal tract inhibits the same motor activities that are facilitated by the pontine reticulospinal tract. Both tracts receive input from regions of the motor cortex.

Descending fibres involved with visceral and autonomic activities emanate from groups of cells at various levels of the brainstem. For example, hypothalamic nuclei project to visceral nuclei in both the medulla oblongata and the spinal cord; in the spinal cord these projections terminate upon cells of the intermediolateral cell column in thoracic, lumbar, and sacral segments. Preganglionic parasympathetic neurons originating in the oculomotor nuclear complex in the midbrain project not only to the ciliary ganglion but also directly to spinal levels. Some of these fibres reach lumbar segments of the spinal cord, most of them terminating in parts of laminae I and V. Pigmented cells in the isthmus, an area of the rostral pons, form a blackish-blue region known as the locus ceruleus; these cells distribute the neurotransmitter norepinephrine to the brain and spinal cord. Fibres from the locus ceruleus descend to spinal levels without crossing and are distributed to terminals in the anterior horn, the intermediate zone, and the dorsal horn. Other noradrenergic cell groups in the pons, near the motor nucleus of the facial nerve, project uncrossed noradrenergic fibres that terminate in the intermediolateral cell column (that is, lamina VII of the lateral horn). Postganglionic sympathetic neurons associated with this system have direct effects upon the cardiovascular system. Cells in the nucleus of the solitary tract project crossed fibres to the phrenic nerve nucleus (in cervical segments three through five), the intermediate zone, and the anterior horn at thoracic levels; these innervate respiratory muscles.

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Where do stem cells come from? Learn the basics of master cells to better understand their therapeutic potential.

In this article:

Where do stem cells come from? You have probably heard of thewonders of stem cell therapy. Not only do stem cells make research for future scientific breakthroughs possible, but they also provide the basis for many medical treatments today. So, where exactly are they from, and how are they different from regular cells? The answer depends on the types of stem cells in question.

There are two main types of stem cells adult and embryonic:

Beyond the two broader categories, there are sub-categories. Each has its own characteristics. For researchers, the different types of stem cells serve specific purposes.

Many tissues throughout the adult human body contain stem cells. Scientists previously believed adult stem cells to be inferior to human embryonic stem cells for therapeutic purposes. Theydid not believe adult stem cells to be as versatile as embryonic stem cells (ESCs), because they are not capable of becoming all 200 cell types within the human body.

While this theoryhas notbeen entirely disproved, encouraging evidence suggests that adult stem cells can develop into a variety of new types of cells. They can also affect repair through other mechanisms.

In August 2017, the number of stem cell publications registered in PubMed, a government database, surpassed 300,000. Stem cells are also being explored in over 4,600 cell therapy clinical trials worldwide. Some of the earliest forms of adult stem cell use include bone marrow and umbilical cord blood transplantation.

It should be noted that while the term adult stem cell is used for this type of cell, it is not descriptive of age, because adult stem cells can come from children. The term simply helps to differentiate stem cells derived from living humans as opposed to embryonic stem cells.

Embryonic stem cells are controversial because they are made from embryos that are created but not used by fertility clinics.

Because adult stem cells are somewhat limited in the cell types they can become, scientists developed a way to genetically reprogram cells into what is called an inducedpluripotent stem cell or iPS cell. In creating inducedpluripotent stem cells, researchers hope to blend the usefulness of adult stem cells with the promise of embryonic stem cells.

Both embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) are known as pluripotent stem cells.

Pluripotent stem cells are a type of cell that has the capacity to divide indefinitely and create any cell found within the three germ layers of an organism: ectoderm (cells forming the skin and nervous system), endoderm (cells forming pancreas, liver, endocrine gland, and gastrointestinal and respiratory tracts), and mesoderm (cells forming connective tissues, and other related tissues, muscles, bones, most of the circulatory system, and cartilage).

Embryonic stem cells can grow into a much wider range of cell types, but they also carry the risk of immune system rejection in patients. In contrast, adult stem cells are more plentiful, easier to harvest, and less controversial.

Embryonic stem cells come from embryos harvested shortly after fertilization (within 4-5 days). These cells are made when the blastocysts inner cell mass is transferred into a culture medium, allowing them to develop.

At 5-6 days post-fertilization, the cells within the embryo start to specialize. At this time, they no longer are able to become all of the cell types within the human body. They are no longer pluripotent.

Because they are pluripotent, embryonic stem cells can be used to generate healthy cells for disease patients. For example, they can be grown into heart cells known as cardiomyocytes. These cells may have the potential to be injected into an ailing patients heart.

Harvesting stem cells from embryos is controversial, so there are guidelines created by the National Institutes of Health (NIH) that allow the public to understand what practices are not allowed.

Scientists can harvest perinatal stem cells from a variety of tissues, but the most common sources include:

The umbilical cord attaches a mother to her fetus. It is removed after birth and is a valuable source of stem cells. The blood it contains is rich in hematopoietic stem cells (HSC). It also contains smaller quantities of another cell type known as mesenchymal stem cells (MSCs).

The placenta is a large organ that acts as a connector between the mother and the fetus. Both placental blood and tissue are also rich in stem cells.

Finally, there is amniotic fluid surrounding a baby while it is in utero. It can be harvested if a pregnant woman needs a specialized kind of test known as amniocentesis. Both amniotic fluid and tissue contain stem cells, too.

Adult stem cells are usually harvested in one of three ways:

The blood draw, known as peripheral blood stem cell donation, extracts the stem cells directly from a donors bloodstream. The bone marrow stem cells come from deep within a bone often a flat bone such as the hip. Tissue fat is extracted from a fatty area, such as the waist.

Embryonic donations are harvested from fertilized human eggs that are less than five days old. The embryos are not grown within a mothers or surrogates womb, but instead, are multiplied in a laboratory. The embryos selected for harvesting stem cell are created within invitro fertilization clinics but are not selected for implantation.

Amniotic stem cells can be harvested at the same time that doctors use a needle to withdraw amniotic fluid during a pregnant womans amniocentesis. The same fluid, after being tested to ensure the babys health, can also be used to extract stem cells.

As mentioned, there is another source for stem cells the umbilical cord. Blood cells from the umbilical cord can be harvested after a babys birth. Cells can also be extracted from the postpartumhuman placenta, which is typically discarded as medical waste following childbirth.

The umbilical cord and the placenta are non-invasive sources of perinatal stem cells.

People who donate stem cells through the peripheral blood stem cell donor procedure report it to be a relativelypainless procedure. Similar to giving blood, the procedure takes about four hours. At a clinic or hospital, an able medical practitioner draws the blood from the donors vein in one of his arms using a needle injection. The technician sends the drawn blood into a machine, which extracts the stem cells. The blood is then returned to the donors body via a needle injected into the other arm. Some patients experience cramping or dizziness, but overall, its considered a painless procedure.

If a blood stem cell donor has a problem with his or her veins, a catheter may be injected in the neck or chest. The donor receives local anesthesia when a catheter-involved donation occurs.

During a bone marrow stem cell donor procedure, the donor is put under heavy sedation in an operating room. The hip is often the site chosen to harvest the bone marrow. More of the desired red marrow is found in flat bones, such as those in the pelvic region. The procedure takes up to two hours, with several extractions made while the patient is sedated. Although the procedure is painless due to sedation, recovery can take a couple of weeks.

Bone marrow stem cell donation takes a toll on the donorbecause it involves the extraction of up to 10 percent of the donors marrow. During the recovery period, the donors body gradually replenishes the marrow. Until that happens, the donor may feel fatigued and sore.

Some clinics offer regenerative and cosmetic therapies using the patients own stem cells derived from the fat tissue located on the sides of the waistline. Considered a simple procedure, clinics do this for therapeutic reasons or as a donation for research.

Stem cells differ from the trillions of other cells in your body. In fact, stem cells make up only a small fraction of the total cells in your body. Some people have a higher percentage of stem cells than others. But, stem cells are special because they are the mothers from which specialized cells grew and developed within us. When these cells divide, they become daughters. Some daughter cells simply self-replicate, while others form new kinds of cells altogether. This is the main way stem cells differ from other body cells they are the only ones capable of generating new cells.

The ways in which stem cells can directly treat patients grow each year. Regenerative medicine now relies heavily on stem cell applications. This type of treatment replaces diseased cells with new, healthy ones generated through donor stem cells. The donor can be another person or the patient themselves.

Sometimes, stem cells also exert therapeutic effects by traveling through the bloodstream to sites that need repair or by impacting their micro-environment through signaling mechanisms.

Some types of adult stem cells, like mesenchymal stem cells (MSCs), are well-known for exerting anti-inflammatory and anti-scarring effects. MSCs can also positively impact the immune system.

Conditions and diseases which stem cell regeneration therapy may help include Alzheimers disease, Parkinsons disease, and multiple sclerosis (MS). Heart disease, certain types of cancer, and stroke victims may also benefit in the future. Stem cell transplant promises advances in treatment for diabetes, spinal cord injury, severe burns, and osteoarthritis.

Researchers also utilize stem cells to test new drugs. In this case, an unhealthy tissue replicates into a larger sample. This method enables researchers to test various therapies on a diseased sample, rather than on an ailing patient.

Stem cell research also allows scientists to study how both healthy and diseased tissue grows and mutates under various conditions. They do this by harvesting stem cells from the heart, bones, and other body areas and studying them under intensive laboratory conditions. In this way, they get a better understanding of the human body, whether healthy or sick.

With the following stem cell transplant benefits, its not surprising people would like to try the therapy as another treatment option.

Physicians harvest stem cell from either the patient or a donor. For an autologous transplant, there is no risk of transferring any disease from another person. For an allogeneic transplant, the donor is meticulously screened before the therapy to make sure they are compatible with the patient and have healthy sources of stem cells.

One common and serious problem of transplants is the risk of rejecting the transplanted organs, tissues, stem cells, and others. With autologous stem cell therapy, the risk is avoided primarily because it comes from the same person.

Because stem cell transplants are typically done through infusion or injection, the complex and complicated surgical procedure is avoided. Theres no risk of accidental cuts and scarring post-surgery.

Recovery time from surgeries and other types of treatments is usually time-consuming. With stem cell therapy, it could only take about 3 months or less to get the patient back to their normal state.

As the number of stem cell treatments dramatically grew over the years, its survival rate also increased. A study published in the Journal of Clinical Oncology showed there was a significant increase in survival rate over 12 years among participants of the study. The study analyzed results from over 38,000 stem cell transplants on patients with blood cancers and other health conditions.

One hundred days following transplant, the researchers observed an improvement in the survival rate of patients with myeloid leukemia. The significant improvements we saw across all patient and disease populations should offer patients hope and, among physicians, reinforce the role of blood stem cell transplants as a curative option for life-threatening blood cancers and other diseases.

With the information above, people now have a better understanding of the answer to the question Where do stem cells come from? Stem cells are a broad topic to comprehend, and its better to go back to its basics to learn its mechanisms. This way, a person can have a piece of detailed knowledge about these master cells from a scientific perspective.

If you found this blog valuable, subscribe to BioInformants stem cell industry updates.

As the first and only market research firm to specialize in the stem cell industry, BioInformant research is cited by The Wall Street Journal, Xconomy, AABB, and Vogue Magazine. Bringing you breaking news on an ongoing basis, we encourage you to join more than half a million loyal readers, including physicians, scientists, executives, and investors.

What do you understand aboutthe basics of stem cells? Share your thoughts in the comments section below.

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Where Do Stem Cells Come From? | Basics Of Stem Cell Therapy

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Spinal Cord Stem Cells Comments Off on Where Do Stem Cells Come From? | Basics Of Stem Cell … | January 26th, 2019

Modern medicine has still not managed to crack the problem of spinal cord injuries that result in significant paralysis or loss of functional status.

There are numerous factors that influence the inability to restore movement or autonomous bodily control to these patients. A prominent example of these is the inability to cultivate new neurons that make up and power the spinal cord.

However, some researchers have claimed that they have successfully induced generic human stem cells to differentiate into stem cells that apply more specifically to the spine.

Why We Cant Repair a Spine (Yet)

Strategies involving the implantation of any kind of donor cell to regenerate or recreate damaged spinal tissue have not shown much success. Furthermore, some medical researchers also believe that such forays into regenerative medicine are not feasible, in terms of costs and resources, at this point. Therefore, this area of cell-based therapy is still very much at the development stage.

The goals of many current projects in this area revolve around the restoration of the motor function in subjects (mostly rodents in animal models). This requires the full re-generation and reinstatement of the corticospinal tract (CST), an important spinal region that communicates with the relevant cortices in the brain.

A limited number of reports claim to have achieved this. However, this leaves the rest of the spine un-addressed, which may have a residual effect on movement and other functions.

New Direction in Cell-Based Therapy for Spinal Injuries

In the past, CST-based trials used grafts of multipotent cells, which were progenitor cells rather than true stem cells.

However, a newer study has documented a technique in which human pluripotent stem cells were used, which could differentiate into all the cells a spinal section needs, and not just the CST ones.

Reportedly, these neural stem cells further diversified into different types of neurons. Therefore, it can be concluded that neural stem cells may be capable of more complete regeneration of missing or damaged spinal tissue in living subjects.

The researchers behind the apparent breakthrough claimed that their cells were capable of doing this in an appropriate model. However, the research was conducted by causing the stem cells to grow a customized spinal graft, which was then transplanted using the model.

A transverse spinal section showing some functions of various spinal region. (Source: Public Domain)

The scientists claimed that these grafts integrated well with the sections of pre-existing spinal tissue upstream and downstream of the graft location. These consisted of various intra-, supra- and cortico-spinal networks of neural connections, which allowed peripheral nervous functions, including movement, under normal circumstances.

In addition, it is necessary for these networks to distinguish between the dorsal (or backward-facing) and ventral portions of the spine. This is because these regions send different signals to the brain in different directions in the average healthy spine. The researchers asserted that their spinal grafts were indeed capable of these distinctions.

The scientists behind this project reported that their models subjects gained increased functional status as a result of receiving one of these grafts. However, it can be assumed that these assertions are getting slightly ahead of their time, in terms of being approved as a real-world treatment.

The researchers also noted that their new spinal stem cells and the neurons that they differentiate into can be used as an excellent in vitro model for the neurobiology of the spine. In addition, the cells may also now be used to test other novel potential treatments for spinal disorders.

Highlights

The scientists behind this project collaborated across the departments of neurosciences and psychiatry & neurology at the University of California (Los Angeles), as well as the San Diego Veterans Administrations Healthcare System. The team published their findings in an August 2018 issue of Nature Methods.

The researchers also hope that future work on this model could lead to the application of their cells to next-generation regenerative medicine that focuses on the spine and how to repair it after injury or damage.

Therefore, we may be able to look forward to a time, in which improved medicine could restore paraplegic patients to the health and autonomy that they may cherish.

Top Image: The spine is an important component of the human nervous system. (Source: Pixabay)

References

H. Kumamaru, et al. (2018) Generation and post-injury integration of human spinal cord neural stem cells. Nature Methods.

S. A. Goldman. (2016) Stem and Progenitor Cell-Based Therapy of the Central Nervous System: Hopes, Hype, and Wishful Thinking. Cell Stem Cell. 18:(2). pp.174-188.

K. Kadoya, et al. (2016) Spinal cord reconstitution with homologous neural grafts enables robust corticospinal regeneration. Nat Med. 22:(5). pp.479-487.

Deirdre ODonnell

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share WHAT ARE STEM CELLS?

Mesenchymal stem cells are specialized cells that naturally grow in our body and can differentiate into bone, cartilage or fat cells. They are widely used in medicine as a natural healing solution to effectively treat orthopedic conditions including the spine and major joints (like the shoulder, hip, knee, ankle, etc.).

There are many benefits of stem cell therapy, including but not limited to:

The human body has multiple sites for stem cells to repair degenerated and injured structures. We have found that obtaining stem cells from the hip bone (iliac bone) is easily performed within minutes. After the stem cells are obtained, minutes later they can be used for treatment in our outpatient state-of-the-art-facility. Regenerative stem cell injections are performed using image guidance (i.e. ultrasound or fluoroscopy) to ensure accurate placement of the stem cells. Once the affected area is sterilized and numbed with a novocaine-type solution, stem cells are injected and begin regenerating and strengthening weakened joints.

Stem cell injections are most commonly used for treatment of the following conditions:

Stem cell injections are designed to heal and strengthen damaged tissue, therefore pain relief is typically noticed several weeks after the procedure. Final relief is seen approximately two to three months after the entire treatment protocol has been completed.

In most cases, patients respond very well to just one treatment. Some patients, depending on the severity of the injury, may benefit from two to three injections over the course of 12 months.

As with all procedures, there are minor risks associated with stem cell injections including infection, bleeding, or nerve damage. It is important to note that there is no risk of allergic reaction since you are using your bodys own healing factors. The physicians at Virginia Spine Institute will always recommend the safest and most efficient procedures for our patients, however, your physician will review any possible risks associated with this treatment prior to administering.

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Regenerative Stem Cell Therapy | Treatment for Back Pain | VSI

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Stem cell-filled implants helped repair spinal cord damage in animals, according to a study led by UC San Diego scientists. If all goes well, the implants with neural stem cells could be ready for testing in human patients in a few years.

Rats with completely severed spinal cords regained some voluntary motion after getting the implants, said the study, published Monday in the journal Nature Medicine. The study is online at j.mp/ucsdspine.

They were able to move the joints of their lower legs, said study co-author Dr. Mark Tuszynski. They couldn't support their weight very well, but they could move the legs around the joints. If one were to project what this means to humans, it might mean that the legs are still weak, but that with an assist they would be able to control them.

The next step is to repeat the procedure in monkeys, said Tuszynski, director of the Translational Neuroscience Institute at UC San Diego School of Medicine.

If successful, it would fulfill one of the biggest hopes for stem cell therapy.

Repairing spinal cord injuries has long been a major goal of the states stem cell program, the California Institute for Regenerative Medicine, or CIRM. The agency was formed in 2004 with the passage of Prop. 71. The late actor Christopher Reeve figured prominently in the campaign for Prop. 71.

While there have been encouraging reports of individual spinal cord injury patients benefiting from stem cell-based therapy, no such treatment has been approved as safe and effective. So scientists at UCSD and elsewhere are trying to make a treatment that can be reliably replicated.

Another study with neural stem cells without the implant has shown benefit in monkeys after spinal cord injury, Tuszynski said. This work is closer to the clinical stage.

The rat implants were constructed by 3D bioprinting of a biologically compatible hydrogel, which is mostly made up of water. These 2-millimeter-wide implants contain tiny channels that guide growth of neural stem cells, also called neural progenitor cells. The cells matured into neurons and reconnected severed nerves, Tuszynski said.

Besides guiding growth, the implants allowed blood vessels to grow, nourishing the newly formed cells. This process, called vascularization, has been hard to achieve in growing new tissue. But with the biologically compatible implants, vascularization occurred spontaneously.

The implants also protected the neural stem cells from the inflammatory damage associated with a fresh injury.

This is a nice marriage of the technology of bioengineering and 3D printing with stem cell biology to treat a really important human disease that needs better therapy, Tuszynski said.

Implants can be quickly custom-made for human spinal cord injuries, according to the study. Researchers bioprinted implants of 4 centimeters within 10 minutes. These were made according to MRI scans of real human spinal cord injuries.

Two other UCSD study authors, Shaochen Chen and Wei Zhu, have co-founded a San Diego startup, Allegro 3D, to commercialize the rapid bioprinting technology. Allegro is doing this independently of the spinal cord injury research.

We will be talking to people to find a partner, said Chen, a founding co-director of the Biomaterials and Tissue Engineering Center at UC San Diego. It takes money, time and effort, so it won't be done in a university setting.

The neural stem cells are produced from a lineage of human embryonic stem cells. This lineage was one of the original certified while George W. Bush was president.

The researchers treat the cells with their own cocktail of growth chemicals that coax them into becoming spinal cord neural stem cells, which cant become any other kind of cell besides types of spinal cord cells.

When these cells are placed at the injury site, with or without the implant, the stem cells complete development.

Importantly, these cells grow axons, the long fibers that carry nerve signals, Tuszynski said. They extend out of the implant and into the spinal cord below the injury. They relay signals that cross synapses, the tiny gaps between nerve cells.

Because the cells arent from the patient, the body may tend to reject them. So patients receiving these cells will need immunosuppressive therapy, he said.

Newer classes of immune-suppressing drugs now available are safer and better tolerated than earlier ones, Tusyznski said.

We think patients would stay on them for awhile, he said.

The research was funded by the National Institutes of Health; the California Institute for Regenerative Medicine; and the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation.

UCSD also hosts ongoing stem cell-based clinical trials for spinal cord injuries and other diseases. More information can be found at the Sanford Stem Cell Clinical Center, reachable at j.mp/ucsdssc.

Related reading

3D printed implant promotes nerve cell growth to treat spinal cord injury

Biomimetic 3D-printed scaffolds for spinal cord injury repair

Allegro 3D

Stem cell-based spinal cord therapy expanded to more patients

Stem cells have become keys to unlock how life develops

UCSD finds possible treatment for paralysis

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